An increasing number of applications use nanospecie-fluorescent labeling technology; however, no established guidelines are available to warrant their safety for potential clinical use. Here, rTg4510 transgenic mice and their littermate controls were injected with fluorogold, a nanospecie tracer, or phosphate buffered saline (PBS) targeted to the right amygdala. No significant abnormal behavior was detected in any mice injected with PBS. After fluorogold injection, however, rTg4510 mice displayed persistent left-sided neurological deficits and left circling behavior for up to 14 days post-injection, while control mice demonstrated a transient syndrome. Mortality occurred only in rTg4510 mice and statistically significant differences appeared independent of age. An immunofluorescent study revealed TUNEL positive cells that were heavily and extensively distributed in the periamygdalar region that overlapped with the fluorogold deposit region in rTg4510 mice, whereas control mice showed only sporadic distribution of TUNEL-positive cells. Colocalization of TUNEL and caspase-3 active peptide immunoreactivity was identified in a subset of the cells, indicating an involvement of caspase-dependent apoptotic mechanisms. In conclusion, fluorogold induces damage in the central nervous system most noticeably in mice over-expressing human mutant tau.